br STAR Methods br Acknowledgments We thank Simcere Pharmace

STAR★Methods
Acknowledgments We thank Simcere Pharmaceuticals, Nanjing, China, for providing a rabbit anti-VEGF neutralizing monoclonal antibody. We thank Dr. Schlisio in the Ludwig Institute for Cancer Research, Karolinska Institute, for assistance with hypoxia assay. Y.C.’s laboratory is supported through research grants from the Swedish Research Council; the Swedish Cancer Foundation; the Karolinska Institute Foundation; the Karolinska Institute Distinguished Professor Award; the Torsten Soderbergs Foundation; the Tore Nilsons Foundation; the Ruth and Richard Julin Foundation; the Ogonfonden Foundation; Wera Ekströms Foundation; the Lars Hiertas Minne Foundation; National Natural Science Foundation of China (project no. 81773059); the International Research Fund for Subsidy of Kyushu University School of Medicine Alumni; the Martin Rinds Foundation; the Maud and Birger Foundation; the Alex and Eva Wallströms Foundation; the Robert Lundbergs Memorial Foundation; the Swedish Diabetes Foundation; the Swedish Children Cancer Foundation; the European Research Council (ERC) advanced grant ANGIOFAT (project no. 250021); the Knut Alice Wallenberg Foundation; and the NOVO Nordisk Foundation for the advanced grant. G.N. is supported by the Shenzhen Science and Technology Innovation Committee (project nos. JCYJ20170306091452714, GJHZ20170313172439851, and JCYJ20170413162242627).
Introduction Preeclampsia (PE) is a complex hypertensive pregnancy syndrome that affects between 2 and 7% of pregnant women after the 20th week, and which may appear superimposed on chronic Tirofiban hydrochloride monohydrate (CH), for instance. It is characterized by systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg in hypertensive women, followed by proteinuria≥300mg/L in urine/24h [1], [2], [3]. Moreover, the presence of thrombocytopenia (platelets<100,000/mμl), renal failure (creatinine≥1.1mg/dl) or impairment of liver function (doubled normal concentration of oxaloacetic transaminase and pyruvate transaminase), pulmonary edema, as well as cerebral and visual disturbances, accompanied by hypertension [4] in the absence of proteinuria, are other criteria for the diagnosis of PE [3], [5]. Eclampsia, from the Greek eklampsis (lightning), refers to the sudden onset of persistent headache, photophobia, scotomas, epigastric pain or pain in the right upper quadrant, as well as seizures [3], [6]. It is noteworthy that the impairment of hepatic and renal function may lead to hemolysis, which is characterized by increased plasma level of lactate dehydrogenase, persistent increase in the level of liver enzymes and in thrombocytopenia, which is called HELLP (hemolysis, elevated liver enzymes and low platelets) [7]; and which may lead to intense inflammatory response, endothelial injury, generalized vascular resistance [8], disseminated intravascular coagulation, hepatic infarction, cerebral vascular disease, premature placental abruption and oliguria [2], [3], for instance. Different risk factors for PE have been discussed in the literature, and predisposing factors may include the following: African descent, obesity, short stature, nutritional deficiencies, previous CH (prevalent in up to 35% of the cases) or gestational hypertension [9] in previous pregnancies, heredity, urinary tract infections, diabetes mellitus, autoimmune diseases, hydatidiform mole, multiple pregnancy, and fetal macrosomia [10], [11], [12], [13]. According to Chaiworapongsa et al. [15], other factors include primiparity in young women, which is associated with intolerance of the maternal immune system to paternal alloantigens present in the seminal fluid and in the sperm; heredity, represented by the presence of genetic variations in collagen α1-chain (I), interleukin-1α (IL-1α), urokinase-type plasminogen activator receptor; maternal-fetal incompatibility of lymphotoxin-α, von Willebrand factor, and α2 chain of collagen [14]; mutations in factor V Leiden, in human leukocyte antigen, in endothelial nitric oxide synthases, and in angiotensin converting enzyme [15].